Alternative splicing within the I-II loop controls surface expression of T-type Ca(v)3.1 calcium channels.
Molecular diversity of T-type/Ca(v)3 Ca2+ channels is created by expression of three genes and alternative splicing of those genes. Prompted by the important role of the I-II linker in gating and surface expression of Ca(v)3 channels, we describe here the properties of a novel variant that partially deletes this loop. The variant is abundantly expressed in rat brain, even exceeding transcripts with the complete exon 8. Electrophysiological analysis of the Delta8b variant revealed enhanced current density compared to Ca(v)3.1a, but similar gating. Luminometry experiments revealed an increase in the expression of Delta8b channels at the plasma membrane. We conclude that alternative splicing of Ca(v)3 channels regulates surface expression and may underlie disease states in which T-channel current density is increased.
Shcheglovitov
Aleksandr
A
Department of Pharmacology, University of Virginia, Charlottesville, VA 2908, USA.
Vitko
Iuliia
I
Bidaud
Isabelle
I
Baumgart
Joel P
JP
Navarro-Gonzalez
Manuel F
MF
Grayson
T Hilton
TH
Lory
Philippe
P
Hill
Caryl E
CE
Perez-Reyes
Edward
E
D017398:Alternative Splicing; D000818:Animals; D020747:Calcium Channels, T-Type / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism*; D014644:Genetic Variation; D008297:Male; D008564:Membrane Potentials; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion
C500994:Cacna1g protein, rat; D020747:Calcium Channels, T-Type